Relationship between FH tumor-suppressor gene and aerobic glycolysis (Warburg effect)
Project/Area Number |
26462426
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Urology
|
Research Institution | Dokkyo Medical University |
Principal Investigator |
Kamai Takao 獨協医科大学, 医学部, 教授 (80316562)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 腎細胞癌 / HLRCC / Akt / Nrf2 / aerobic glycolysis / FH遺伝子 / 腎癌 |
Outline of Final Research Achievements |
The main findings of the present study were as follows: 1) A higher standard glucose uptake value (SUVmax) on 18F-FDG-PET was correlated with higher expression of phosphorylated Akt(Ser-473) in the primary tumor. A higher SUVmax and increased expression of phosphorylated Akt(Ser-473) was associated with a higher pT stage,and metastasis, as well as shorter overall survival in RCC patients. 2) Targeted next-generation sequencing revealed that fumarate hydratase (fumarase, FH) mutation and loss of the second allele were completely identical between blood and tumor samples in Hereditary Leiomyomatosis and Renal Cell Cancer(HLRCC)cancer patients. Furthermore, surgically resected samples showed high expression of phosphorylated Akt(Ser-473) as well as nuclear factor E2-related factor 2 (Nrf2), suggesting that FH mutation plays a direct role in a metabolic shift to aerobic glycolysis), and increased an anti-oxidant response phenotype in HLRCC-associated kidney cancer.
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Report
(4 results)
Research Products
(2 results)